Assessment of the Efficacy of Bevacizumab in Combination With Folfiri as Second-line Treatment in Patients Suffering From an Advanced Inoperable Poorly Differentiated Neuroendocrine Carcinoma of an Unknown or Gastroentero-pancreatic Primary Cancer

NCT02820857 | Completed Phase 2 DMC

• 2 other identifiers: 69HCL14_04422016-001305-16
• Study Type: interventional
• Target: 153
• Locations: 1 country
• Sites: 26

Brief Summary

Poorly differentiated neuroendocrine carcinomas (NEC) are a sub-group of aggressive neuroendocrine neoplasms (NEN). The most common primary sites are broncho-pulmonary and digestive. The gastroentero-pancreatic NECs (GEP-NEC) represent 7-21% of all of the NENs. Recent data on the initial presentation of GEP-NEC have been reported in two retrospective studies and a French cohort study. No standard second-line treatment has been defined for NECs. Despite a very negative prognosis, these NECs have a certain amount of chemosensitivity, close to that of bronchial NECs. Multiple-drug therapies such as Folfiri, or Folfox, or single drug treatments such as temozolomide are the proposed options but with a low level of proof Bevacizumab associated with a cytotoxic chemotherapy has shown promising results in well differentiated neuroendocrine tumors (NET), known for being hypervascular. The efficacy of bevacizumab has also been suggested in patients with NEC, but never in the context of a phase II study. Its combination with Folfiri is efficient and well tolerated in metastatic colorectal cancer. The combination Folfiri-bevacizumab potentially represents an optimized treatment compared to chemotherapy with only Folfiri. No phase II or III studies have reported results for these patients, and no on-going phase II or III trial have been identified to date. The main objective of this study is to show that, after the failure of a first-line chemotherapy using platinum-etoposide, the combination Folfiri-bevacizumab allows significant prolongation of overall survival in adult patients with GEP-NEC.

Conditions

Neuroendocrine Carcinomas

Keywords

Gastroentero-pancreatic neuroendocrine carcinomas; Second-line treatment; Bevacizumab; Folfiri

Outcome Measures

Primary Outcomes (1)

• Proportion of patients alive

  The primary endpoint is the proportion of patients alive 6 months after treatment

  6 months after treatment

Study Arms (2)

Folfiri-bevacizumab

EXPERIMENTAL

Patient treated with a combination Folfiri-bevacizumab. Treatment every 2 weeks (D1 = D15)

Drug: Folfiri-bevacizumab

Folfiri

ACTIVE COMPARATOR

Patient treated with Folfiri only. Treatment every 2 weeks (D1 = D15)

Drug: Folfiri

Interventions

Folfiri-bevacizumab DRUG

Patient treated with a combination Folfiri-bevacizumab. Treatment every 2 weeks (D1 = D15)

Folfiri-bevacizumab

Folfiri DRUG

Patient treated with Folfiri only. Treatment every 2 weeks (D1 = D15)

Folfiri

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Man or woman aged ≥ 18 years old,
• Poorly differentiated neuroendocrine carcinoma (NEC) from a gastrointestinal tract (from esophagus to anal canal) and biliopancreatic primary or an unknown primary cancer, locally advanced and/or metastatic,
• Centralized review of the diagnostic by a consulting pathologist specializing in NET (TENPATH network),
• Recommendation of a second-line chemotherapy after progression, documented using the RECIST criteria v.1.1, and after a first-line chemotherapy treatment by cisplatin (or carboplatin) + etoposide or in the event of progression in the 6 months following the discontinuation of this first-line treatment,
• Recommendation of a second-line chemotherapy for the refractory patient or contraindicated for platinum-etoposide chemotherapy
• Patients presenting at least one measurable target lesion according to the RECIST criteria v.1.1, in an area not previously irradiated,
• General condition ≤ 2 (WHO),
• Patient of child bearing age accepting to use an effective contraception during treatment and until 6 months after the last administration,
• Patient who signed the informed consent form.

You may not qualify if:

• Relating to the tumor, the patient, and previous treatment:
• Well differentiated neuroendocrine tumor
• Mixed tumor, except if the NEC component is \> 70%, the patient is eligible,
• First-line chemotherapy other than cisplatin (or carboplatin) and etoposide,
• All malignant disease in the three years before randomization, with the exception of basal cell carcinoma or in situ cancer treated for curative purposes,
• A pregnant or breastfeeding woman,
• Lack of efficient contraception (for men or women of reproductive age),
• All medical, geographical, social, and psychological conditions or a legal situation that will not allow the patient to finish the study or sign an informed consent form,
• Relating to the chemotherapy (Folfiri):
• Any of the following uncontrolled progressive diseases in the 6 months before randomization: liver failure, renal insufficiency, respiratory distress, congestive heart failure (NYHA III-IV), unstable angina, myocardial infarction, significant arrhythmia,
• Known deficiency in dihydropyrimidine dehydrogenase,
• Known Gilbert's syndrome,
• Total bilirubin level \>1.5x the upper limit of normal (ULN); AST (Aspartate transaminase) and/or ALT (Alanine transaminase) \>5x ULN; TP \<50%;
• Neutrophils \<1.5x109/l, platelets \<100x109/l, hemoglobin \<9 g/dl,
• Chronic uncontrolled diarrhea, unresolved intestinal occlusion or subocclusion,

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (26)

Service d'Hépato-Gastroenterologie et Oncologie Digestive, Hôpital Sud, CHU d'Amiens

Amiens, 80054, France

Location

Service d'Hépatogastroentérologie, CHU d'Angers

Angers, 49933, France

Location

Service d'Oncologie et Radiothérapie, Institut Sainte Catherine

Avignon, 84918, France

Location

Service de Gastroentérologie et Oncologie Digestive, Hôpital Avicenne

Bobigny, 93000, France

Location

Service de Gastroentérologie et Pancréatologie, Hôpital Beaujon, APHP

Clichy, 92118, France

Location

Service de Gastroentérologie, CHU Henri Mondor

Créteil, 94000, France

Location

Service d'Hépato-Gastroentérologie et Oncologie Digestive, CHU de Dijon

Dijon, 21000, France

Location

Service d'Hépatogastroentéologie, Hôpital Michallon, CHU de Grenoble

Grenoble, 38043, France

Location

Département de Cancérologie Urologique et Digestive, Centre Oscar Lambret

Lille, 59020, France

Location

Département de cancérologie médicale - Groupe des tumeurs endocrines, Centre Léon Bérard

Lyon, 69008, France

Location

Service d'Oncologie Médicale - Hôpital Edouard Herriot - Hospices Civils de Lyon

Lyon, 69437, France

Location

Département d'Oncologie Médicale, Institut Paoli Calmettes

Marseille, 13009, France

Location

Service d'Hépato-Gastroentérologie et d'Oncologie Digestive, Hôpital de la Timone, APHM

Marseille, 13365, France

Location

Service d'Oncologie Médicale, Hôpital Saint Eloi, CHU de Montpellier

Montpellier, 34298, France

Location

Service d'Hépatogastroentérologie, CHR d'Orléans

Orléans, 45067, France

Location

Département d'Oncologie Médicale, Hôpital Saint-Antoine

Paris, 75012, France

Location

Service de Gastroentérologie, Hôpital Cochin, APHP

Paris, 75014, France

Location

Service d'Hépato-Gastroenterologie et Oncologie Digestive, Hôpital Européen Georges Pompidou, APHP

Paris, 75015, France

Location

Service d'Hépato-Gastroentérologie et d'Oncologie Digestive, Hôpital Haut Lévêque, CHU Bordeaux

Pessac, 33604, France

Location

Pôle Régional de Cancérologie, CHU de Poitiers

Poitiers, 86021, France

Location

Service d'Hépato-Gastroentérologie et Cancérologie, Hôpital Robert Debré, CHU de Reims

Reims, 51100, France

Location

Service d'Hépatogastroentérologie, Hôpital Pontchaillou, CHU de Rennes

Rennes, 35000, France

Location

Service de Gastroentérologie, CHU de Rouen

Rouen, 76031, France

Location

Service de Gastro-Entérologie, Hôpital Nord, CHU de ST-Etienne

Saint-Priest-en-Jarez, 42270, France

Location

Service d'Oncologie Médicale, Hôpital Civil, CHU de Strasbourg

Strasbourg, 67200, France

Location

Service d'Oncologie Endocrinienne, Institut Gustave Roussy

Villejuif, 94805, France

Location

Related Publications (1)

• Walter T, Lievre A, Coriat R, Malka D, Elhajbi F, Di Fiore F, Hentic O, Smith D, Hautefeuille V, Roquin G, Perrier M, Dahan L, Granger V, Sobhani I, Mineur L, Niccoli P, Assenat E, Scoazec JY, Le Malicot K, Lepage C, Lombard-Bohas C. Bevacizumab plus FOLFIRI after failure of platinum-etoposide first-line chemotherapy in patients with advanced neuroendocrine carcinoma (PRODIGE 41-BEVANEC): a randomised, multicentre, non-comparative, open-label, phase 2 trial. Lancet Oncol. 2023 Mar;24(3):297-306. doi: 10.1016/S1470-2045(23)00001-3. Epub 2023 Feb 2.

  PMID: 36739879 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Neuroendocrine

Interventions

IFL protocol

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 29, 2016
• First Posted: July 1, 2016
• Study Start: September 4, 2017
• Primary Completion: August 8, 2022
• Study Completion: August 24, 2024
• Last Updated: September 3, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

FR (26)